The potential of lead and mercury in their inorganic and/or organic states as a health hazard to man, animals and plants is well documented. However, there are no multidisciplinary data available pinpointing the primary target of the toxic action of lead and mercury at the cellular and/or subcellular level in the central nervous system. Recent findings in this laboratory have identified the ultrastructural alterations of nerve cells components and associated trace metal changes in the brain which are induced by Pb and Hg exposure. Our multidisciplinary approach will attempt to correlate (1) the sequential cytopathogenesis of specific nerve cell organelles with (2) the sequential accumulation of toxic metals (Pb, Hg) and related shifts of essential trace metals (Cu, Fe, Zn) and (3) the sequential interference with certain metallo-enzymes and acid phosphatase using quantitative and qualitative methods. The significance of all obtained data will be statistically evaluated. This expanded grant proposal is a multidisciplinary effort to provide a basis for better understanding of the subcellular mechanism of the toxic action of metals in the central nervous system.